Paradoxical effects of pyruvate on cardiac contractile function under normal and high glucose in ventricular myocytes

Impaired energy fuel supply and metabolism contribute to the cardiac contractile dysfunctions in diabetes. Pyruvate, a metabolic product of glycolysis and an oxidizable fuel in myocardium, has been demonstrated to enhance cardiac contractile function and alleviate hyperglycemic status. The present study was designed to examine the impact of pyruvate supplementation on cardiac mechanical function under normal glucose (NG) and high glucose (HG) conditions. Isolated adult rat ventricular myocytes were maintained in NG (5.5mM) or HG (25.5mM) medium for 24h in the absence or presence of pyruvate (5mM). Contractile indices were measured with an IonOptix edge-detection system including peak shortening (PS), maximal velocity of shortening/relengthening (+/-dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), area underneath shortening (A(con)) and relengthening (A(relax)). Myocytes maintained in HG medium displayed abnormal mechanical function simulating in vivo diabetes. These abnormalities included reduced PS, +/-dL/dt, prolonged TPS/TR(90) associated with enhanced A(con) and A(relax) compared to NG myocytes. Interestingly, these HG-induced mechanical dysfunctions were completely abolished by co-incubation of pyruvate. However, NG myocytes developed mechanical defects reminiscent of those of HG following co-incubation with pyruvate. These data suggest that pyruvate may paradoxical affect cardiac mechanical function under different glucose settings and therefore warrant caution when applying pyruvate therapeutically.